Vertebral fractures are the most common complication of osteoporosis and are associated with significant morbidity and increased mortality. It is estimated that 30-50% of individuals over age 50 have at least one vertebral fracture, and the presence of an initial fracture increases risk of subsequent fracture 5-12 fold relative to other osteoporotic individuals matched for age and bone mineral density (BMD), but with no pre-existing fracture. This phenomenon is known as the 'vertebral fracture cascade', and despite the large negative impact of vertebral fractures on the health and well being of the elderly population, the mechanisms underlying the increased risk of future fracture are unclear. The aim of this study is to investigate the contribution of altered biomechanics to the vertebral fracture cascade. Our hypothesis is that an initial vertebral fracture alters the geometry of the spine such that spinal compressive loading is increased during activities of daily living, thereby increasing risk of subsequent vertebral fracture. To test our hypothesis, we will quantify the effect of vertebral fracture on spinal curvature using CT imaging data from a large-community based cohort consisting of approximately 3500 individuals age 31 - 83, and then use a novel model of the thoracic and lumbar spine to explore how fractured spinal geometries affect mechanical loading and fracture risk in the spine. Knowledge of the mechanisms underlying the vertebral fracture cascade will contribute to improved clinical management of individuals with osteoporosis in the following ways: 1) Fracture risk may be better estimated by understanding how factors other than bone mineral density contribute to fracture;and 2) The results will provide improved understanding of possible efficacy of interventions, such as exercise and/or vertebral augmentation, directed at maintaining normal spinal curvature. PUBLIC HEALTH RELEVANCE: This project aims at understanding the contribution of altered biomechanics to the vertebral fracture cascade, which is a devastating cycle that leads to significant morbidity and increased mortality in the elderly. Knowledge of the mechanisms underlying the vertebral fracture cascade will contribute to improved clinical management of individuals with osteoporosis in the following ways: 1) Fracture risk may be better estimated by understanding how factors other than bone mineral density contribute to fracture;and 2) The results will provide improved understanding of possible efficacy of interventions, such as exercise and/or vertebral augmentation, directed at maintaining normal spinal curvature.